scholarly journals 2363 Inducing anti-tumor immunity in colorectal cancer

2018 ◽  
Vol 2 (S1) ◽  
pp. 15-16
Author(s):  
Jonathan B. Mitchem ◽  
Yue Guan ◽  
Mark Daniels ◽  
Emma Teixeiro
Keyword(s):  
Colorectal Cancer ◽  
Statistical Analysis ◽  
T Cell ◽  
Tumor Growth ◽  
Tumor Immunity ◽  
Suppressor Cells ◽  
The United States ◽  
Cytotoxic T Cell ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Bearing

OBJECTIVES/SPECIFIC AIMS: Despite significant advances in screening and treatment, colorectal cancer is the second leading cancer killer in the United States today. Some of the most promising recent developments in cancer therapy have come from immune-based therapy. Immune-based therapy, however, has shown limited utility in patients with colorectal cancer. Studies have previously shown that certain chemotherapy regimens may be more effective in combination with immune-based therapy due to induction of inflammation in the tumor microenvironment. In this study, we sought to determine how standard chemotherapy (FOLFOX) affects the generation of antigen-specific anti-tumor immunity in colorectal cancer. METHODS/STUDY POPULATION: To determine the how antigen-specific immunity and T cell responses are affected by FOLFOX, we utilized a model antigen expressing murine colon cancer cell line syngeneic to C57BL/6 (MC38-CEA). Treatment was initiated when tumor size reached 50 mm2. Mice were treated with either vehicle (PBS), 5-Fluorouracil (5-FU), Oxaliplatin, or combination (FOLFOX). Antigen-specific cytotoxic T cell (tet+Tc) were detected using Db-CEA-tetramer obtained from the NIH-tetramer core facility. Flow cytometry was performed for phenotypic analysis and tetramer positivity. Tumor growth was measured using standard caliper measurements. Statistical analysis was performed using t-test for continuous variables and ANOVA was used when comparing multiple groups. Statistical analysis was performed using SPSS. All arms were completed with n=3–7. RESULTS/ANTICIPATED RESULTS: To determine how systemic treatment with chemotherapy affects cytotoxic T cell development (Tc), we established that we could detect antigen-specific Tc (tet+Tc) in the spleen, tumor, and draining lymph nodes of tumor-bearing mice. After establishing that the system worked appropriately, tumor-bearing mice were treated with different chemotherapy regimens and tumor growth was monitored. As expected, the combination of FOLFOX was significantly better than either drug individually (2-way ANOVA, p<0.01). FOLFOX therapy also showed a significant (p<0.05) increase in the number of tumor-associated tet+Tc, and tet+Tc expressing phenotypic markers of effector (Te) and resident memory (Trm) subsets. Tumor-associated tet+Tc highly expressed PD-1 (>50%); however, this was not significantly different between treatment or vehicle arms. Since 5-FU, one component of FOLFOX has previously shown a selective reduction of myeloid-derived suppressor cells, we also investigated the myeloid compartment. There were no significant differences in conventional or plasmacytoid dendritic cells, myeloid-derived suppressor cells, or tumor-associated macrophages. DISCUSSION/SIGNIFICANCE OF IMPACT: The future of cancer care involves multi-modality care tailored to patients. To more effectively combine therapy it is critical that we understand how currently utilized therapy works. In this study, we show that the primary chemotherapy regimen utilized in colorectal cancer increases tumor-associated antigen-specific cytotoxic T cells and the majority of these cells are PD-1 positive. This suggests that FOLFOX may work in concert with immune-based therapy when selected appropriately. Further study is warranted to determine optimal combination therapy and ways to maximize anti-tumor immunity in order to improve the treatment of patients with this deadly disease.

scholarly journals Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Cancer and Immunotherapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1170
Author(s):  
Mithunah Krishnamoorthy ◽  
Lara Gerhardt ◽  
Saman Maleki Maleki Vareki
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Cancer Immunotherapy ◽  
Tumor Immunity ◽  
Cancer Progression ◽  
Suppressor Cells ◽  
T Cell Immunity ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Immunity ◽  
Promote Tumor Growth

The primary function of myeloid cells is to protect the host from infections. However, during cancer progression or states of chronic inflammation, these cells develop into myeloid-derived suppressor cells (MDSCs) that play a prominent role in suppressing anti-tumor immunity. Overcoming the suppressive effects of MDSCs is a major hurdle in cancer immunotherapy. Therefore, understanding the mechanisms by which MDSCs promote tumor growth is essential for improving current immunotherapies and developing new ones. This review explores mechanisms by which MDSCs suppress T-cell immunity and how this impacts the efficacy of commonly used immunotherapies.

scholarly journals Down-regulation of PLCγ2–β-catenin pathway promotes activation and expansion of myeloid-derived suppressor cells in cancer

2013 ◽  
Vol 210 (11) ◽  
pp. 2257-2271 ◽  
Author(s):  
Aude-Hélène Capietto ◽  
Seokho Kim ◽  
Dominic E. Sanford ◽  
David C. Linehan ◽  
Masaki Hikida ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Down Regulation ◽  
Tumor Bearing ◽  
Promote Tumor Growth ◽  
Negative Role ◽  
Cell Inhibition

Myeloid-derived suppressor cells (MDSCs) favor tumor promotion, mainly by suppressing antitumor T cell responses in many cancers. Although the mechanism of T cell inhibition is established, the pathways leading to MDSC accumulation in bone marrow and secondary lymphoid organs of tumor-bearing hosts remain unclear. We demonstrate that down-regulation of PLCγ2 signaling in MDSCs is responsible for their aberrant expansion during tumor progression. PLCγ2−/− MDSCs show stronger immune-suppressive activity against CD8+ T cells than WT MDSCs and potently promote tumor growth when adoptively transferred into WT mice. Mechanistically, PLCγ2−/− MDSCs display reduced β-catenin levels, and restoration of β-catenin expression decreases their expansion and tumor growth. Consistent with a negative role for β-catenin in MDSCs, its deletion in the myeloid population leads to MDSC accumulation and supports tumor progression, whereas expression of β-catenin constitutively active reduces MDSC numbers and protects from tumor growth. Further emphasizing the clinical relevance of these findings, MDSCs isolated from pancreatic cancer patients show reduced p-PLCγ2 and β-catenin levels compared with healthy controls, similar to tumor-bearing mice. Thus, for the first time, we demonstrate that down-regulation of PLCγ2–β-catenin pathway occurs in mice and humans and leads to MDSC-mediated tumor expansion, raising concerns about the efficacy of systemic β-catenin blockade as anti-cancer therapy.

scholarly journals Immunomodulation by Inflammation during Liver and Gastrointestinal Tumorigenesis and Aging

2021 ◽  
Vol 22 (5) ◽  
pp. 2238
Author(s):  
Nao Nagai ◽  
Yotaro Kudo ◽  
Daisuke Aki ◽  
Hayato Nakagawa ◽  
Koji Taniguchi
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Antitumor Immunity ◽  
Suppressor Cells ◽  
Treg Cells ◽  
Cytotoxic T Cell ◽  
Myeloid Derived Suppressor Cells ◽  
Age Related ◽  
Immunosuppressive Tumor Microenvironment ◽  
Pro Inflammatory Cytokines

Chronic inflammation is thought to promote tumorigenesis and metastasis by several mechanisms, such as affecting tumor cells directly, establishing a tumor-supporting microenvironment, enhancing tumor angiogenesis, and suppressing antitumor immunity. In this review, we discuss the recent advances in our understanding of how inflammation induces the immunosuppressive tumor microenvironment, such as increasing the level of pro-inflammatory cytokines, chemokines, and immunosuppressive molecules, inducing immune checkpoint molecules and cytotoxic T-cell exhaustion, and accumulating regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs). The suppression of antitumor immunity by inflammation is especially examined in the liver and colorectal cancer. In addition, chronic inflammation is induced during aging and causes age-related diseases, including cancer, by affecting immunity. Therefore, we also discuss the age-related diseases regulated by inflammation, especially in the liver and colon.

scholarly journals The mechanism of the premetastatic niche facilitating colorectal cancer liver metastasis generated from myeloid-derived suppressor cells induced by the S1PR1–STAT3 signaling pathway

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Qi Lin ◽  
Li Ren ◽  
Mi Jian ◽  
Pingping Xu ◽  
Jun Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
T Cell ◽  
Liver Metastasis ◽  
Signaling Pathway ◽  
Mouse Models ◽  
Poor Prognosis ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Premetastatic Niche

Abstract The tumor-derived factors involved in the expansion and accumulation of myeloid-derived suppressor cells (MDSCs) in metastatic dissemination of colorectal cancer (CRC) to the liver has not been studied. Immunohistochemistry was used to detect sphingosine-1-phosphate receptor 1 (S1PR1) and signal transducer and activator of transcription-3 (STAT3) in human colorectal tumors. IL-6 and interferon-γ were detected by enzyme-linked immunosorbent assay (ELISA). Tumor growth, invasion, and migration were evaluated by MTT, transwell, and wound healing assays, respectively. Subcutaneous tumor-bearing and CRC liver metastasis (CRLM) nude mouse models were constructed. The percentage of MDSCs was measured using multicolor flow cytometry. Western blot assay was used to evaluate S1PR1 and p-STAT3 expression in MDSCs after separation from the liver and tumor by magnetic antibody. T-cell suppression assay was detected by carboxyfluorescein succinimidyl ester (CFSE). Aberrant co-expressed S1PR1 and p-STAT3 was correlated with metachronous liver metastasis and poor prognosis in CRC. A mutual activation loop between S1PR1 and STAT3 can enhance CRC cell proliferation, migration, and invasion in vitro and in vivo. The expression of p-STAT3 and its downstream proteins can be regulated by S1PR1. p-STAT3 was the dependent signaling pathway of S1PR1 in the promotion of cell growth and liver metastasis in CRC. The level of IL-6 and the associated MDSCs stimulated by the S1PR1–STAT3 correlated with the number of liver metastatic nodes in the CRLM mouse models and patients. Increased CD14+HLA-DR−/low MDSCs from CRLM patients inhibited autologous T-cell proliferation and predict poor prognosis. The S1PR1–STAT3–IL-6–MDSCs axis operates in both tumor cells and MDSCs involved in the promotion of growth and liver metastasis in CRC. MDSCs induced by S1PR1–STAT3 in CRC cells formed the premetastatic niche in the liver can promote organ-specific metastasis.

scholarly journals Independent mechanisms of T cell-suppression by subpopulations of myeloid-derived suppressor cells (MDSC) in tumor-bearing hosts

2013 ◽  
Vol 1 (Suppl 1) ◽  
pp. P193
Author(s):  
Patrick L Raber ◽  
Paul Thevenot ◽  
Rosa Sierra ◽  
Dorota Wyczechowska ◽  
Maria E Ramirez ◽  
...  
Keyword(s):  
T Cell ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Bearing ◽  
T Cell Suppression ◽  
Cell Suppression

scholarly journals MYd88 Blockade Caused Reduction of PDL1 on Tumor Infiltrating MDSCs in a Murine Model of Melanoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1012-1012
Author(s):  
Parvin Forghani ◽  
Edmund K Waller
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Immunity ◽  
Murine Model ◽  
Suppressor Cells ◽  
B16 Melanoma ◽  
Myeloid Derived Suppressor Cells ◽  
Antitumor Effects ◽  
Arginase 1 ◽  
Significant Difference

Abstract Introduction: Myeloid differentiation primary response gene 88 (Myd 88) is an important adaptor molecule for the activation of NADPH oxidase and regulation of arginase-1, which are responsible for the suppressive function of myeloid-derived suppressor cells (MDSCs). Blockade of Myd88 signaling induces antitumor effects in mice by skewing the immunosuppressive function of myeloid-derived suppressor cells. As the PD-L1/PD-1 axis has been characterized as a potent inhibitor of immune activation, particularly through inhibition of effector T cell function, we characterized the effect of Myd88 on checkpoint expression on tumor-infiltrating MDSC/T cells in a murine model melanoma. Methods: Pathogen-free 8-10-week-old WT(B6-background) and Myd 88−/− mice that been backcrossed to a C57BL/6 genetic background were challenged with 1 × 106 B16 (F1) tumor cells s.c. On day 14, mice were sacrificed and spleen and tumors were removed and digested into single-cell suspensions, blocked with anti-FcR mAbs and analyzed for surface and intracellular staining by flow cytometry. We analyzed CD11b+/Gr-1+hi/int myeloid cells subsets and T cells in the blood, spleen and tumors of mice by flow cytomery. Results: The growth of B16 melanoma tumor was significantly slower in Myd 88−/− mice compared with WT mice. No significant difference between two groups was found in the frequency of absolute number of MDSC subsets and expression of PDL1 check-point marker on spleen-derived MDSC subsets. In contrast CD4(+) and C8(+) T cells residing in spleens of Myd88(-/-) mice showed increased expression of TNF-α/IFN-α and GrZB compared with T cells from wild-type mice following short-term activation with PMA/iono. Of note, the frequencies and absolute numbers of infiltrating CD11b+/Gr1+ MDSC in tumor-bearing Myd 88−/− mice were lower than those in WT mice. Also we found that viable CD11b+/Gr1+ MDSC subsets from WT mice expressed higher level of PD-L1 compared with MDSCs from Myd 88−/− mice in concordance with the reduced expression of PD-1 on tumor infiltrating CD4+ T cells in Myd 88−/− mice. Collectively, the profile of PD-L1 and PD-1 expression in tumor microenvironments is favorably altered to enhance adaptive immune response in myd 88 KO vs WT mice harboring B16 melanoma. Conclusion: The results of this study provide further evidence that blocking Myd 88 signaling increases anti tumor immunity against melanoma, and that the enhanced immunity can be explained, in part, by reduction of expression PDL1/PD1 immune checkpoint molecules. Considering the importance of tumor-infiltrating MDSCs in regulating anti tumor immunity in the tumor microenvironment, our findings could provide insight into the design of new therapeutics targeting Myd 88. Further experiments are needed to show how alteration in profile of PDL1 checkpoint expression on MDSCs influences anti-tumor T cell responses. Disclosures No relevant conflicts of interest to declare.

scholarly journals Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin

2019 ◽  
Vol 25 (1) ◽  
pp. 46-59 ◽  
Author(s):  
Young Suk Lee ◽  
Eduardo Davila ◽  
Tianshu Zhang ◽  
Hugh P Milmoe ◽  
Stefanie N Vogel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Suppressor Cells ◽  
Arginase Activity ◽  
T Cell Proliferation ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Bearing ◽  
And Function

Myeloid-derived suppressor cells (MDSCs) inhibit T cell responses and are relevant to cancer, autoimmunity and transplant biology. Anti-thymocyte globulin (ATG) is a commonly used T cell depletion agent, yet the effect of ATG on MDSCs has not been investigated. MDSCs were generated in Lewis Lung Carcinoma 1 tumor-bearing mice. MDSC development and function were assessed in vivo and in vitro with and without ATG administration. T cell suppression assays, RT-PCR, flow cytometry and arginase activity assays were used to assess MDSC phenotype and function. MDSCs increased dramatically in tumor-bearing mice and the majority of splenic MDSCs were of the polymorphonuclear subset. MDSCs potently suppressed T cell proliferation. ATG-treated mice developed 50% fewer MDSCs and these MDSCs were significantly less suppressive of T cell proliferation. In vitro, ATG directly bound 99.6% of MDSCs. CCR7, L-selectin and LFA-1 were expressed by both T cells and MDSCs, and binding of LFA-1 was inhibited by ATG pre-treatment. Arg-1 and PD-L1 transcript expression were reduced 30–40% and arginase activity decreased in ATG-pretreated MDSCs. MDSCs were bound and functionally inhibited by ATG. T cells and MDSCs expressed common Ags which were also targets of ATG. ATG may be helpful in tumor models seeking to suppress MDSCs. Alternatively, ATG may inadvertently inhibit important T cell regulatory events in autoimmunity and transplantation.

Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice

Blood ◽  
2008 ◽  
Vol 111 (12) ◽  
pp. 5457-5466 ◽  
Author(s):  
Yasushi Sawanobori ◽  
Satoshi Ueha ◽  
Makoto Kurachi ◽  
Takeshi Shimaoka ◽  
James E. Talmadge ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Development ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Bearing ◽  
Promote Tumor Growth ◽  
Brdu Labeling ◽  
And Migration ◽  
Stimulating Factor

Abstract Tumor growth is associated with aberrant myelopoiesis, including the accumulation of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) that have the potential to promote tumor growth. However, the identity, growth, and migration of tumor-associated MDSCs remain undefined. We demonstrate herein that MDSCs at tumor site were composed primarily of bone marrow-derived CD11b+Gr-1hiLy-6Cint neutrophils and CD11b+Gr-1int/dullLy-6Chi macrophages. Unexpectedly, in vivo bromodeoxyuridine (BrdU) labeling and parabiosis experiments revealed that tumor-infiltrating macrophages were replenished more rapidly than neutrophils. CCR2 deficiency caused striking conversion of infiltrating cellular dominance from macrophages to neutrophils in the tumor with the excessive production of CXCR2 ligands and granulocyte-colony stimulating factor in the tumor without affecting tumor growth. Overall, our data established the identity and dynamics of MDSCs in a tumor-bearing host mediated by chemokines and elucidated unexpected effects of the paucity of macrophages on tumor development.

scholarly journals Myeloid-Specific SHP-2 Ablation Induces Robust Anti-Tumor Immunity That Is Not Further Enhanced By PD-1 Blockade

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Anthos Christofides ◽  
Natalia M Tijaro-Ovalle ◽  
Halil-Ibrahim Aksoylar ◽  
Rinku Pal ◽  
Abdelrahman AA Mahmoud ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Tumor Immunity ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Tumor Bearing ◽  
Suppressor Function ◽  
Emergency Myelopoiesis ◽  
Myeloid Progenitors

PD-1 is a T cell inhibitor for which blocking agents have achieved success as anti-cancer therapeutics. The current view is that cancer limits host immune responses by upregulating PD-L1 in the tumor microenvironment thereby causing PD-1 ligation and inactivation of CD8+ Teff cells. Recently, we determined that PD-1 alters the differentiation of myeloid progenitors during cancer-mediated emergency myelopoiesis. We found that PD-1 is expressed in granulocyte/macrophage progenitors (GMP), which accumulate during cancer-driven emergency myelopoiesis and give rise to myeloid-derived suppressor cells (MDSC) that promote tumor growth. In tumor-bearing mice with myeloid-specific PD-1 ablation, accumulation of GMP and MDSC was prevented, while output of effector myeloid cells was increased. PD-1-mediated T cell inactivation is attributed to the function of SHP-2 phosphatase, which is activated by recruitment to PD-1 cytoplasmic tail. Temporal activation of SHP-2 is critical for myeloid cell fate. Activating SHP-2 mutations prevent myeloid cell differentiation and lead to the accumulation of immature myelocytes and development of leukemia. To determine whether PD-1-mediated inhibition of anti-tumor immunity relies on SHP-2-mediated effects in T cells or myeloid cells, we generated mice with conditional targeting of the Ptpn11 gene (encoding for Shp-2) and selectively eliminated Shp-2 in T cells (Shp-2fl/flLckCre) or myeloid cells (Shp-2fl/flLysMCre). No significant difference in tumor growth was observed between control Shp2fl/fl and Shp-2fl/flLckCre mice bearing B16-F10 melanoma. Strikingly, Shp-2fl/flLysMCre mice had significantly diminished tumor growth that was not further decreased by anti-PD-1 antibody, in contrast to control Shp-2fl/fl mice in which anti-PD-1 treatment significantly reduced tumor size. To determine how Shp-2 ablation affected the properties of myeloid cells, we examined CD11b+Ly6ChiLy6G- monocytic (M-MDSC), CD11b+Ly6CloLy6G+ polymorphonuclear (PMN-MDSC), CD11b+F4/80+ tumor-associated macrophages (TAM) and CD11c+MHCII+ dendritic cells (DC). No quantitative differences were observed in these myeloid subsets in tumor bearing mice among the different groups. However, M-MDSC from Shp-2fl/flLysMCre mice had elevated expression of CD86 and IFNγ, consistent with effector differentiation. Suppression assays, by measuring antigen-specific responses of OTI transgenic T cells, showed significantly attenuated suppressor function of MDSC isolated from tumor-bearing Shp-2f/fLysMCre mice compared to control or Shp-2f/fLckCre mice. CD38 is a key mediator of MDSC-mediated immunosuppression. It is an ADP-ribosyl cyclase that has ectoenzyme and receptor functions, is induced early during differentiation of myeloid progenitors by retinoic acid receptor alpha (RARα) signaling, and mediates T cell immunosuppression. Because Shp-2 is involved in the differentiation of myeloid progenitors, we examined CD38 expression. We found that expression of CD38 was significantly reduced in MDSC from Shp-2fl/flLysMCre mice compared to control and Shp-2fl/flLckCre-tumor bearing mice. Since the suppressive potency of MDSC is decreased by autophagy, and SHP-2 has been implicated in regulating autophagy in cancer cells, we examined autophagy of MDSC in our system. Assessment of autophagy in ex vivo isolated MDSC, using Cyto-ID that stains the autophagosome membrane and indicates autophagic activity, showed enhanced autophagy in MDSC isolated from tumor bearing Shp-2fl/flLysMCre mice compared to control or Shp-2fl/flLckCre mice. Enhanced autophagy was also detected in bone marrow-derived MDSC from Shp-2fl/flLysMCre mice as determined by accumulation of LC3B-II and p62 during culture under conditions of starvation-induced stress. Consistent with the diminished MDSC suppressor function, myeloid cell-specific Shp-2 ablation in tumor-bearing mice induced an increase of CD8+ T cells showing an effector phenotype with improved functionality, despite preserved expression of PD-1 and Shp-2. Together these results indicate that inhibition of PD-1-mediated SHP-2 activation in myeloid progenitors, thereby preventing the accumulation of immature immunosuppressive MDSC and promoting the differentiation of effector myeloid cells, might be a previously unidentified mechanism by which PD-1 blockade mediates anti-tumor function. Disclosures No relevant conflicts of interest to declare.

scholarly journals Myeloid-Derived Suppressor Cells: A New and Pivotal Player in Colorectal Cancer Progression

2020 ◽  
Vol 10 ◽  
Author(s):  
Kai Yin ◽  
Xueli Xia ◽  
Ke Rui ◽  
Tingting Wang ◽  
Shengjun Wang
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Suppressor Cells ◽  
Therapeutic Strategies ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Bearing ◽  
Human Malignancy ◽  
Novel Approaches ◽  
Colorectal Cancer Progression

Colorectal cancer (CRC) remains a devastating human malignancy with poor prognosis. Of the various factors, immune evasion mechanisms play pivotal roles in CRC progression and impede the effects of cancer therapy. Myeloid-derived suppressor cells (MDSCs) constitute an immature population of myeloid cells that are typical during tumor progression. These cells have the ability to induce strong immunosuppressive effects within the tumor microenvironment (TME) and promote CRC development. Indeed, MDSCs have been shown to accumulate in both tumor-bearing mice and CRC patients, and may therefore become an obstacle for cancer immunotherapy. Consequently, numerous studies have focused on the characterization of MDSCs and their immunosuppressive capacity, as well as developing novel approaches to suppress MDSCs function with different approaches. Current therapeutic strategies that target MDSCs in CRC include inhibition of their recruitment and alteration of their function, alone or in combination with other therapies including chemotherapy, radiotherapy and immunotherapy. Herein, we summarize the recent roles and mechanisms of MDSCs in CRC progression. In addition, a brief review of MDSC-targeting approaches for potential CRC therapy is presented.

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